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Comparison of the molecular dynamics and calculated binding free energies for nine FDA-approved HIV-1 PR drugs against subtype B and C-SA HIV PR.
MedLine Citation:
PMID:  23017010     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We report the first account of a comparative analysis of the binding affinities of nine FDA approved drugs against subtype B as well as the South African subtype C HIV PR (C-SA). A standardised protocol was used to generate the inhibitor/C-Sa PR complexes with the relative positions of the inhibitors taken from the corresponding X-ray structures for subtype B complexes. The dynamics and stability of these complexes were investigated using MD calculations. Average relative binding free energies for these inhibitors were calculated from the MD simulation using the MM-GBSA method. The calculated energies followed a similar trend to the reported experimental binding free energies. Post-dynamics hydrogen bonding and electrostatic interaction analysis of the inhibitors with both subtypes reveal similar interactions. Most inhibitors show slightly weaker binding affinities for C-SA PR. MD studies demonstrated increased flap movement for C-SA PR, which can perhaps explain the weaker affinities. This study serves as a standardised platform for optimising the design of future more potent HIV C-SA PR inhibitors. © 2012 John Wiley & Sons A/S.
Authors:
Shaimaa M Ahmed; Hendrik G Kruger; Thirumala Govender; Glenn E M Maguire; Yasien Sayed; Mahmoud Ibrahim; Previn Naicker; Mahmoud E S Soliman
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-28
Journal Detail:
Title:  Chemical biology & drug design     Volume:  -     ISSN:  1747-0285     ISO Abbreviation:  Chem Biol Drug Des     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262549     Medline TA:  Chem Biol Drug Des     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Affiliation:
School of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Wits 2050, South Africa School of Chemistry, University of Manchester, Oxford Road, Manchester M139PL, United Kingdom Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
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